A number of viral inhibitors occur in the body. Some inhibitors, including antibodies and interferons, are induced as a consequence of viral infection. Other inhibitors spontaneously occur in the uninfected host. They range from narrow to broad antiviral activity and inhibit viruses by diverse mechanisms.
In recent years, we studied three broadly active viral inhibitors that are produced spontaneously in the body or in cell culture. We tentatively have named them (a) contact-blocking viral inhibitor (CVI), (b) UTI-.alpha., and (c) UTI-.beta.. These naturally produced inhibitors may serve as host defenses against a number of virus groups.
The three inhibitors, CVI, UTI-.alpha. and UTI-.beta., share one major characteristic: broad antiviral activity. The distinguishing features of these three inhibitors are their molecular size, essential chemical composition, thermal and chemical stability, and physiologic site of occurrence.
CVI was first detected unexpectedly during characterization of interferon preparations from tissue culture. The interferon preparations under study contained a second inhibitor (CVI) with properties that clearly differentiated it from interferon. Some of these properties not only distinguish this inhibitor from other previously reported inhibitors but also had surprising molecular properties. The distinguishing properties of CVI include: inhibition of attachment of many viruses to cells; apparent molecular size of 3000-4000 kDa; essential peptide and carbohydrate structure; high stability to physical and chemical agents; reversibility of inhibition; and production in a number of cell cultures.
UTI-.alpha. was discovered unexpectedly when we surveyed body fluids and tissue extracts for CVI which we had found previously in cell cultures. Many body fluids and tissue extracts contained a broadly active viral inhibitor but with properties clearly distinct from those of CVI. Those properties which distinguished UTI-.alpha. from CVI are: inhibiting of replication of some viruses (as well as viral attachment for most viruses); molecular size between 500 and 3000 daltons; essential carbohydrate structure; extreme thermal stability; and presence in many body fluids and tissue extracts.
UTI-.beta. was recently discovered in human sera when it was found that the broad spectrum antiviral activity in normal human serum was distinct from CVI and from UTI-.alpha..
Other virus inhibitors have been reported from human serum. These include inhibitors of myxoviruses (alpha or Francis, beta or Chu, gamma, and C), inhibitors of influenza, NDV, and mumps (Krizanova et al., "Serum Inhibitors of Myxoviruses," Curr. Too Microbiol. Immunol. 47:125 (1969) and Karzon, "Non-specific Viral Inactivating Substance (VIS) in Human and Mammalian Sera," J. Immunol. 76:454-463 (1956)), poxviruses (Kitamura et al., "Studies on a Heat-Labile Variola Virus Inhibitor in Normal Sera II. Further Characterization of the Inhibitor and its Activity," Intervirology 1:288-296 (1973)), togaviruses (Shortridge et al., "Human Serum Lipoproteins as Inhibitors of Haemagglutination for Selected Togaviruses," J. Gen. Virol. 23:113-116 (1974)), coronavirus (Gerna et al., "Human Coronavirus OC-43 Serum Inhibitor and Neutralizing Antibody by a New Plaque-Reduction Assay," Proc. Soc. Exp. Biol. Med. 163:360-366 (1980)), Sendai virus (Suribaldi et al., "Inhibiting Activity of Human Serum Low Density Lipoprotein Toward Sendai Virus," Microbiologics 2:121-128 (1979)), retroviruses (Welsh et al., "Inactivation and Lysis of Oncornaviruses by Human Serum," Virology 74:432-440 (1976)), and rhabdoviruses (Thiry et al., "Factors Which Influence Inactivation of Vesicular Stomatitis Virus by Fresh Human Serum," Virology 87:384-393 (1978)). Normal animal sera also posses a wide spectrum of viral inhibitors, many of which are homologous to those found in human sera. These inhibitors affect adeno, polio, ECHO, arbo, myxo, vaccinia, variola, Rous sarcoma, lymphocytic choriomengititis, measles, and herpes (Allen et al., "Viral Inhibitors in Normal Animal Sera," Tex. Rep. Biol. Med. 16:39-421 (1958)), vesicular stomatitis, encephalomyocarditis, and caprine herpes viruses (Yilma et al., "Preliminary Characterization of a Serum Viral Inhibitor," Am. J. Vet. Res. 46(11):2360-62 (I985)). The properties reported for these inhibitors indicate that they are from CVI, UTI-.alpha. and UTI-.beta..